Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2)

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	Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2)
	Zhang, Rui ; Wang, Zhiguo ; Ling, Baoping ; Liu, Yongjun ; Liu, Chengbu
	2010
发表期刊	MOLECULAR SIMULATION ; Zhang, R; Wang, ZG; Ling, BP; Liu, YJ; Liu, CB.Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2),MOLECULAR SIMULATION,2010,36(2):166-174
摘要	Kir6.2, a key component of the ATP-sensitive potassium channel (K(ATP)), can directly interact with imidazoline derivatives a kind of potential antidiabetic drug. This paper explores the interaction of Kir6.2 with four imidazoline derivatives by using AutoDock and Gromacs programs. The docking results reveal that the binding sites of the four imidazolines are different from each other: Idazoxan lies in a polar active pocket formed by residues H177, G299 and R301; while RX871024 is situated in a hydrophobic pocket composed of residues F168, M169 and I296; as for Efaroxan and Clonidine, residues H175, R177, K67 and W68 constitute the binding pocket. Based on the docking results, the four imidazoline/Kir6.2 complexes with explicit water and infinite lipid bilayer membrane were constructed to perform molecular dynamics (MD) simulation. The results of MD calculation are as follows: dioleoyl phosphatidyl choline bilayer membrane stabilised the structure of these complexes through polar and nonpolar interaction; Idazoxan and RX871024 are stably combined with Kir6.2 in their docking sites; Efaroxan has a minor change in contrast to the docking result; whereas Clonidine has an obvious change compared to docking conformation. The binding sites and interaction modes of these imidazolines with Kir6.2 may provide theoretical support in the pharmacological study of imidazoline drugs.; Kir6.2, a key component of the ATP-sensitive potassium channel (K(ATP)), can directly interact with imidazoline derivatives a kind of potential antidiabetic drug. This paper explores the interaction of Kir6.2 with four imidazoline derivatives by using AutoDock and Gromacs programs. The docking results reveal that the binding sites of the four imidazolines are different from each other: Idazoxan lies in a polar active pocket formed by residues H177, G299 and R301; while RX871024 is situated in a hydrophobic pocket composed of residues F168, M169 and I296; as for Efaroxan and Clonidine, residues H175, R177, K67 and W68 constitute the binding pocket. Based on the docking results, the four imidazoline/Kir6.2 complexes with explicit water and infinite lipid bilayer membrane were constructed to perform molecular dynamics (MD) simulation. The results of MD calculation are as follows: dioleoyl phosphatidyl choline bilayer membrane stabilised the structure of these complexes through polar and nonpolar interaction; Idazoxan and RX871024 are stably combined with Kir6.2 in their docking sites; Efaroxan has a minor change in contrast to the docking result; whereas Clonidine has an obvious change compared to docking conformation. The binding sites and interaction modes of these imidazolines with Kir6.2 may provide theoretical support in the pharmacological study of imidazoline drugs.
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/40947
专题	中国科学院西北高原生物研究所
推荐引用方式 GB/T 7714	Zhang, Rui,Wang, Zhiguo,Ling, Baoping,et al. Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2)[J]. MOLECULAR SIMULATION, Zhang, R; Wang, ZG; Ling, BP; Liu, YJ; Liu, CB.Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2),MOLECULAR SIMULATION,2010,36(2):166-174,2010.
APA	Zhang, Rui,Wang, Zhiguo,Ling, Baoping,Liu, Yongjun,&Liu, Chengbu.(2010).Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2).MOLECULAR SIMULATION.
MLA	Zhang, Rui,et al."Docking and molecular dynamics studies on the interaction of four imidazoline derivatives with potassium ion channel (Kir6.2)".MOLECULAR SIMULATION (2010).